NM_000543.5(SMPD1):c.108GCTGGC[8] (p.38AL[8]) AND multiple conditions

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 26, 2022
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001281392.3

Allele description [Variation Report for NM_000543.5(SMPD1):c.108GCTGGC[8] (p.38AL[8])]

NM_000543.5(SMPD1):c.108GCTGGC[8] (p.38AL[8])

Gene:

SMPD1:sphingomyelin phosphodiesterase 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000543.5(SMPD1):c.108GCTGGC[8] (p.38AL[8])

HGVS:

NC_000011.10:g.6390706GCTGGC[8]
NG_011780.1:g.5282GCTGGC[8]
NM_000543.4:c.132_143dup12
NM_000543.5:c.108GCTGGC[8]MANE SELECT
NM_001007593.3:c.108GCTGGC[8]
NM_001318087.2:c.108GCTGGC[8]
NM_001318088.2:c.-854GCTGGC[8]
NM_001365135.2:c.108GCTGGC[8]
NP_000534.3:p.38AL[8]
NP_001007594.2:p.38AL[8]
NP_001305016.1:p.38AL[8]
NP_001352064.1:p.38AL[8]
NC_000011.9:g.6411935_6411936insGCTGGCGCTGGC
NC_000011.9:g.6411936GCTGGC[8]
NM_000543.4:c.132_143dupGCTGGCGCTGGC
NM_000543.5:c.132_143dupMANE SELECT
NR_027400.3:n.233GCTGGC[8]
NR_134502.2:n.233GCTGGC[8]

Links:

dbSNP: rs3838786

NCBI 1000 Genomes Browser:

rs3838786

Molecular consequence:

NM_001318088.2:c.-854GCTGGC[8] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000543.5:c.108GCTGGC[8] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001007593.3:c.108GCTGGC[8] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001318087.2:c.108GCTGGC[8] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001365135.2:c.108GCTGGC[8] - inframe_insertion - [Sequence Ontology: SO:0001821]
NR_027400.3:n.233GCTGGC[8] - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134502.2:n.233GCTGGC[8] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Niemann-Pick disease, type B
Identifiers:: MONDO: MONDO:0011871; MedGen: C0268243; Orphanet: 77293; OMIM: 607616

Name:: Niemann-Pick disease, type A
Synonyms:: SPHINGOMYELIN LIPIDOSIS; SPHINGOMYELINASE DEFICIENCY
Identifiers:: MONDO: MONDO:0009756; MedGen: C0268242; Orphanet: 77292; OMIM: 257200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001468697	Huiwen Zhang's lab, Shanghai Jiao Tong University School of Medicine, Xinhua Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 30, 2020)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003249670	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 26, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33675270, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001468697

Huiwen Zhang's lab, Shanghai Jiao Tong University School of Medicine, Xinhua Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 30, 2020)

inherited

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003249670

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 26, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.

Hu J, Maegawa GHB, Zhan X, Gao X, Wang Y, Xu F, Qiu W, Han L, Gu X, Zhang H.

Hum Mutat. 2021 May;42(5):614-625. doi: 10.1002/humu.24192. Epub 2021 Mar 19.

PubMed [citation]

PMID:: 33675270

See all PubMed Citations (3)

Details of each submission

From Huiwen Zhang's lab, Shanghai Jiao Tong University School of Medicine, Xinhua Hospital, SCV001468697.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV003249670.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant, c.132_143dup, results in the insertion of 4 amino acid(s) of the SMPD1 protein (p.Ala46_Leu49dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with SMPD1-related conditions (PMID: 33675270). ClinVar contains an entry for this variant (Variation ID: 992676). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 4, 2024

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